A5102892405- Virus-based gene therapy research
- Mosquito-borne diseases and control
- Endoplasmic Reticulum Stress and Disease
- SARS-CoV-2 and COVID-19 Research
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Lipid Membrane Structure and Behavior
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Genomics and Phylogenetic Studies
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- Genetics, Aging, and Longevity in Model Organisms
- DNA Repair Mechanisms
- Transgenic Plants and Applications
- Immunotherapy and Immune Responses
- interferon and immune responses
- Hepatitis C virus research
- RNA regulation and disease
- Infectious Encephalopathies and Encephalitis
- Vector-borne infectious diseases
- Extracellular vesicles in disease
University Hospital Heidelberg
2023-2025
Heidelberg University
2020-2025
University of Geneva
2025
University of Zurich
2012-2022
Life Science Zurich
2014-2017
Vellore Institute of Technology University
2009-2010
SARS-CoV-2 is a novel virus that has rapidly spread, causing global pandemic. In the majority of infected patients, leads to mild disease; however, in significant proportion infections, individuals develop severe symptoms can lead long-lasting lung damage or death. These cases are often associated with high levels pro-inflammatory cytokines and low antiviral responses, which cause systemic complications. Here, we have evaluated transcriptional cytokine secretion profiles detected distinct...
Coronavirus replication is associated with the remodeling of cellular membranes, resulting in formation double-membrane vesicles (DMVs). A DMV-spanning pore was identified as a putative portal for viral RNA. However, exact components and structure SARS-CoV-2 DMV remain to be determined. Here, we investigate by situ cryo-electron tomography combined subtomogram averaging. We identify non-structural protein (nsp) 3 4 minimal required pore, which dependent on nsp3-4 proteolytic cleavage. In...
Positive-strand RNA viruses replicate in close association with rearranged intracellular membranes. For hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these rearrangements comprise endoplasmic reticulum (ER)-derived double membrane vesicles (DMVs) serving as replication sites. Cellular factors involved DMV biogenesis are poorly defined. Here, we show that despite structural similarity of viral DMVs autophagosomes, conventional macroautophagy is...
Double membrane vesicles (DMVs) serve as replication organelles of plus-strand RNA viruses such hepatitis C virus (HCV) and SARS-CoV-2. Viral DMVs are morphologically analogous to formed during autophagy, but lipids driving their biogenesis largely unknown. Here we show that production the lipid phosphatidic acid (PA) by acylglycerolphosphate acyltransferase (AGPAT) 1 2 in ER is important for DMV viral autophagy. Using HCV-replicating cells model, found AGPATs recruited critically contribute...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remodels the endoplasmic reticulum (ER) to form replication organelles, leading ER stress and unfolded protein response (UPR). However, role of specific UPR pathways in infection remains unclear. Here, we found that SARS-CoV-2 causes marginal activation signaling sensor IRE1α its phosphorylation, clustering dense ER-membrane rearrangements with embedded membrane openings, XBP1 splicing. By investigating factors regulated by...
Classical plaque assay measures the propagation of infectious agents across a monolayer cells. It is dependent on cell lysis, and limited by user-specific settings low throughput. Here, we developed Plaque2.0, broadly applicable, fluorescence microscopy-based high-throughput method to mine patho-biological clonal features. Plaque2.0 an open source framework extract information from chemically fixed cells immuno-histochemistry or RNA in situ hybridization, live expressing GFP transgene....
Abstract Persistent viruses cause chronic disease, and threaten the lives of immunosuppressed individuals. Here, we elucidate a mechanism supporting persistence human adenovirus (AdV), virus that can kill patients. Cell biological analyses, genetics chemical interference demonstrate one five AdV membrane proteins, E3-19K glycoprotein specifically triggers unfolded protein response (UPR) sensor IRE1α in endoplasmic reticulum (ER), but not other UPR sensors, such as kinase R-like ER (PERK)...
Remodeling of the cellular endomembrane system by viruses allows for efficient and coordinated replication viral genome in distinct subcellular compartments termed organelles. As a critical step life cycle, organelle formation is an attractive target therapeutic intervention, but factors central to this process are only partially understood. In study, we corroborate that two proteins, nsp3 nsp4, major drivers membrane remodeling SARS-CoV-2 infection. We further report number host cell...
Reporter systems are useful tools for fast and quantitative visualization of virus-infected cells within a host cell population. Here, we describe reporter system that takes advantage virus-encoded proteases expressed in infected to cleave an ER-anchored fluorescent protein fused nuclear localization sequence.
Dengue virus (DENV) is a major human pathogen that can cause hemorrhagic fever and shock syndrome. One important factor of DENV pathogenicity non-structural protein 1 (NS1), glycoprotein secreted from infected cells. Here we study the mode action widely used drug ivermectin, to treat parasitic infections recently shown lower NS1 blood levels in DENV-infected patients. We found ivermectin blocks nuclear transport transcription factors required for expression chaperones support folding...
ABSTRACT Cancer cells are susceptible to oncolytic viruses, albeit variably. Human adenoviruses (HAdVs) widely used agents that have been engineered produce progeny within the tumor and elicit bystander effects. We searched for host factors enhancing effects conducted a targeted RNA interference screen against guanine nucleotide exchange (GEFs) of small GTPases. show unfolded protein response (UPR), which is readily inducible in aggressive cells, enhances melanoma or epithelial cancer cell...
For successful infection of host cells and virion production, enveloped viruses, including Zika virus (ZIKV), extensively rely on cellular lipids. However, how protein-lipid interactions contribute to the viral life cycle remains unclear. Here, we employ a chemo-proteomics approach with bifunctional cholesterol probe show that is closely associated ZIKV structural protein prM. Bioinformatic analyses, reverse genetics alongside photoaffinity labeling assays, atomistic molecular dynamics...
In clonal cultures, not all cells are equally susceptible to virus infection, and the mechanisms underlying this poorly understood. Here, we developed image-based single-cell measurements scrutinize heterogeneity of adenovirus (AdV) infection. AdV delivers, transcribes replicates a linear double-stranded DNA genome in nucleus. We measured abundance viral transcripts using single-molecule RNA fluorescence situ hybridization (FISH) incoming 5-ethynyl-2'-deoxycytidine (EdC)-tagged genomes...
Cell invasion is an initiating event during tumor cell metastasis and essential process development. A screen of C . elegans orthologs genes overexpressed in invasive human melanoma cells has identified several components the conserved DNA pre-replication complex (pre-RC) as positive regulators anchor (AC) invasion. The pre-RC function cell-autonomously G1-arrested AC to promote invasion, independently their role licensing replication origins proliferating cells. While helicase activity...
Human adenoviruses (HAdVs) infect respiratory, gastrointestinal, and urinary tracts give rise to eye infections epidemic keratoconjunctivitis (EKC). They persist in lymphoid tissue cause morbidity mortality immunocompromised people. Treatments with significant postexposure efficacy are not available. Here, we report that inhibition of the cell cycle-dependent kinase 9 (Cdk9) by RNA interference, or compound flavopiridol, blocked HAdV-C2/5, EKC-causing HAdV-D8/37, progeny formation human...
Enveloped viruses fuse with host membranes without affecting cell integrity.Non-enveloped and bacteria penetrate by rupturing endosomal membranes, thereby expose complex-type carbohydrates from the endosome lumen to cytosolic proteins.Here we report on dynamics initial marker analyses of Galectin-3 (Gal3)-positive triggered incoming adenovirus species B/C in HeLa cells.Using mCherry-Gal3 reporter constructs, immuno-labeling, confocal electron microscopy, detected robust signals...
Abstract Coronavirus replication is associated with the remodeling of cellular membranes resulting in formation double-membrane vesicles (DMVs). Recently, a pore spanning DMV was identified as putative portal for viral RNA transcription and products providing novel target antiviral intervention. However, exact components structure SARS-CoV-2 remain to be determined. Here, we investigate pores by situ cryo-electron tomography combined subtomogram averaging. We reveal non-structural proteins...
Abstract In clonal cultures, not all cells are equally susceptible to virus infection. Underlying mechanisms of infection variability poorly understood. Here, we developed image-based single cell measurements scrutinize the heterogeneity adenovirus (AdV) AdV delivers, transcribes and replicates a linear double-stranded DNA genome in nucleus. We measured abundance viral transcripts by single-molecule RNA fluorescence situ hybridization (FISH), incoming ethynyl-deoxy-cytidine (EdC)-tagged...
ABSTRACT Positive-strand RNA viruses have been the etiological agents in several major disease outbreaks over last few decades. Examples of that are flaviviruses, such as dengue virus and Zika cause millions yearly infections spread around globe, coronaviruses, SARS-CoV-2, which is current pandemic. The severity caused by these stresses importance virology research determining mechanisms to limit curb severity. Such studies require molecular tools decipher virus-host interactions develop...
The human hepatitis delta virus (HDV) is a satellite RNA that depends on B (HBV) surface proteins (HBsAg) to assemble into infectious virions targeting the same organ (liver) as HBV. Until recently, evolutionary origin of HDV remained largely unknown. application bioinformatics whole sequence databases lead discoveries HDV-like agents (DLA) and shed light HDV’s evolution, expanding our understanding biology. DLA were identified in heterogeneous groups vertebrates invertebrates, highlighting...